No Association between Single-Nucleotide Polymorphisms of The S1PR1 Gene or Interleukin-17 Levels with Fingolimod Response in A Small Group of Iranian Relapsing-Remitting Multiple Sclerosis Patients: A Case-Control Study.

OBJECTIVE: Multiple sclerosis (MS) has a multi-factorial etiology involving genetic factors. Fingolimod (Gilenya ®, FTY720) modulates the G-protein-coupled sphingosine 1-phosphate (S1P) receptors, S1PR1, 2, 3, 4 and 5. Variation in the human S1PR1 coding sequence results in heterogeneity in the function of the receptor. Interleukin-17, producing CD4+ T cells, tends to be increased after treatment with Fingolimod. The aim of the study was to investigate singlenucleotide polymorphisms (SNPs) in the S1PR1 gene or interleukin-17 (IL-17) levels in a small group of Iranian relapsing-remitting MS patients treated with Fingolimod. MATERIALS AND METHODS: In this case-control study, the genomic DNA of 94 MS patients treated with Fingolimod was extracted and Sanger sequencing was performed on polymerase chain reaction (PCR) products to detect variants in the S1PR1 gene. Quantification of IL-17 from the serum of the patients was performed using a commercially available enzyme-linked immunosorbent assay (ELISA). RESULTS: Among 94 relapsing-remitting MS patients treated with Fingolimod, 69 (73.4%) were responders and 25 (26.6%) were non-responders. There were four novel and five common SNPs in the S1PR1 gene and no significant association between SNP genotype and drug response was detected. In a subset of 34 patients, there was no significant difference in IL-17 serum concentrations before or after treatment and no association with S1PR1 polymorphisms was determined. CONCLUSION: This study is the first in Iran to investigate association between SNPs of the S1PR1 gene or IL-17 levels with fingolimod response in a small group of Iranian relapsing remitting MS patients. There was no association with S1PR1 gene SNPs or IL-17 levels before or after treatment.

Predictors of in-hospital mortality among patients with symptoms of stroke, Mashhad, Iran: an application of auto-logistic regression model.

BACKGROUND: Stroke is the second leading cause of death in adults worldwide. There are remarkable geographical variations in the accessibility to emergency medical services (EMS). Moreover, transport delays have been documented to affect stroke outcomes. This study aimed to examine the spatial variations in in-hospital mortality among patients with symptoms of stroke transferred by EMS, and determine its related factors using the auto-logistic regression model. METHODS: In this historical cohort study, we included patients with symptoms of stroke transferred to Ghaem Hospital of Mashhad, as the referral center for stroke patients, from April 2018 to March 2019. The auto-logistic regression model was applied to examine the possible geographical variations of in-hospital mortality and its related factors. All analysis was performed using the Statistical Package for the Social Sciences (SPSS, v. 16) and R 4.0.0 software at the significance level of 0.05. RESULTS: In this study, a total of 1,170 patients with stroke symptoms were included. The overall mortality rate in the hospital was 14.2% and there was an uneven geographical distribution. The results of auto-logistic regression model showed that in-hospital stroke mortality was associated with age (OR = 1.03, 95% CI: 1.01-1.04), accessibility rate of ambulance vehicle (OR = 0.97, 95% CI: 0.94-0.99), final stroke diagnosis (OR = 1.60, 95% CI: 1.07-2.39), triage level (OR = 2.11, 95% CI: 1.31-3.54), and length of stay (LOS) in hospital (OR = 1.02, 95% CI: 1.01-1.04). CONCLUSION: Our results showed considerable geographical variations in the odds of in-hospital stroke mortality in Mashhad neighborhoods. Also, the age- and sex-adjusted results highlighted the direct association between such variables as accessibility rate of an ambulance, screening time, and LOS in hospital with in-hospital stroke mortality. Thus, the prognosis of in-hospital stroke mortality could be improved by reducing delay time and increasing the EMS access rate.

Medical uses of Carthamus tinctorius L. (Safflower): a comprehensive review from Traditional Medicine to Modern Medicine.

BACKGROUND: Carthamus tinctorius L., known as Kafesheh (Persian) and safflower (English) is vastly utilized in Traditional Medicine for various medical conditions, namely dysmenorrhea, amenorrhea, postpartum abdominal pain and mass, trauma and pain of joints. It is largely used for flavoring and coloring purposes among the local population. Recent reviews have addressed the uses of the plant in various ethnomedical systems. OBJECTIVE: This review was an update to provide a summary on the botanical features, uses in Iranian folklore and modern medical applications of safflower. METHODS: A main database containing important early published texts written in Persian, together with electronic papers was established on ethnopharmacology and modern pharmacology of C. tinctorius. Literature review was performed on the years from 1937 to 2016 in Web of Science, PubMed, Scientific Information Database, Google Scholar, and Scopus for the terms "Kafesheh", "safflower", "Carthamus tinctorius", and so forth. RESULTS: Safflower is an indispensable element of Iranian folklore medicine, with a variety of applications due to laxative effects. Also, it was recommended as treatment for rheumatism and paralysis, vitiligo and black spots, psoriasis, mouth ulcers, phlegm humor, poisoning, numb limbs, melancholy humor, and the like. According to the modern pharmacological and clinical examinations, safflower provides promising opportunities for the amelioration of myocardial ischemia, coagulation, thrombosis, inflammation, toxicity, cancer, and so forth. However, there have been some reports on its undesirable effects on male and female fertility. Most of these beneficial therapeutic effects were correlated to hydroxysafflor yellow A. CONCLUSION: More attention should be drawn to the lack of a thorough phytochemical investigation. The potential implications of safflower based on Persian traditional medicine, such as the treatment of rheumatism and paralysis, vitiligo and black spots, psoriasis, mouth ulcers, phlegm humor, poisoning, numb limbs, and melancholy humor warrant further consideration.

99mTc-TRODAT-1 SPECT Imaging in Early and Late Onset Parkinson's Disease.

OBJECTIVES: 99mTc-TRODAT-1, which binds to the dopamine transporter, could be used to image the dopaminergic system in diagnosis of Parkinson's disease (PD). PD can be classified into two groups: late onset Parkinson's disease (LOPD) and early onset Parkinson's disease (EOPD). In this study we tried to determine the TRODAT SPECT findings in EOPD as compared to LOPD. METHODS: Fifteen patients were studied. The diagnosis of PD was defined by clinical criteria based on UK Parkinson's Disease Society Brain Bank criteria. Six patients whose age at onset of PD were younger than 50 were defined as patients with EOPD and 9 patients with older than 50 years were defined as patients with LOPD. All patients underwent 99mTc-TRODAT Brain SPECT. RESULTS: There was a significant decrease of striatal 99mTc-TRODAT-1 (TRODAT) binding in PD patients in both EOPD and LOPD. No significant difference was noticed between EOPD and LOPD in disease stage and symptoms. In visual analysis, 20 (66.67%) caudate nucleuses had decreased tracer uptake while all 30 (100%) putamens had decreased or absent tracer uptake. No significant difference between EOPD and LOPD was noticed in visual analysis. Striatum, Caudate and Putamen uptake ratio to background were calculated. No significant difference was noticed between EOPD and LOPD in these ratios. However there was significant difference in visual analysis (tracer uptake) as well as in uptake ratio between putamen and caudate nucleuses in both groups (P=0.001). On the other word, we found more diminished uptake in putamen as compared the caudate. Frequency and severity of putamen involvement were much more than caudate. CONCLUSION: 99mTc-TRODAT-1 SPECT imaging showed lower presynaptical dopami-nergical terminals density in both EOPD and LOPD. There was no difference between EOPD and LOPD in TRODAT uptake. Putamen showed more involvement and more diminished TRODAT uptake.

Amantadine and the place of acupuncture in the treatment of fatigue in patients with multiple sclerosis: an observational study.

BACKGROUND: Fatigue is a common symptom in patients with multiple sclerosis (MS). It has significant negative effects on the quality of life of patients with the condition. There are few therapeutic modalities for fatigue, which are also usually not sufficiently effective. The aim of this study was to evaluate the efficacy of acupuncture on this common symptom of patients with MS. METHODS: In this before-and-after clinical trial, 40 patients with definite diagnoses of MS, according to the 'McDonald' criteria, were studied. Patients who had Expanded Disability Status Scale (EDSS) scores greater than 4, or who had another disease that could be potentially responsible for their fatigue, were excluded from the study. In all, 20 patients with fatigue refractory to amantadine underwent 12 sessions of acupuncture. Fatigue was scored according to the Fatigue Severity Scale (FSS). RESULTS: A total of 15 (37.5%) patients with MS with fatigue responded to amantadine. The mean FSS score reduction after 2 months of treatment was 8±4, which was statistically significant (p<0.001). Of the 20 patients who were resistant to amantadine, 5 (25%) responded to acupuncture combined with amantadine treatment. The FSS scores of the 20 patients who were refractory were significantly reduced after this treatment (mean: 13±6, p<0.001). CONCLUSIONS: Acupuncture appears to be associated with benefits for a proportion of patients with fatigue who are resistant to conventional drugs such as amantadine, and this finding justifies further research.